The present invention relates generally to bone structure analysis. More specifically, the present invention relates to a method of analyzing bone structure using magnetic resonance micro imaging (μ-MRI).
Bone is a composite biomaterial designed to provide high static and impact strength. Its inorganic fraction is made up of calcium apatite bound to the osteoid, which consists primarily of type-I collagen. Bone constantly remodels, a term used to indicate a dynamic equilibrium that exists between formation and resorbtion. New bone is deposited by osteoblasts, the bone-forming cells, while old bone is resorbed by osteoclasts, the bone-resorbing cells. Although incompletely understood, bone remodeling allows the structure to adapt to the forces to which it is subjected, but also serves as a mechanism to repair fatigue damage. In the adult skeleton, after cessation of growth, an equal amount of bone is resorbed as new bone is formed, i.e. there is no net bone balance. Bone formation and resorbtion are tightly coupled processes involving a complex interplay of various hormones. This regulation acts in concert with mechanical stimuli mediated by osteocytes, a third type of cell embedded in the bone matrix, that act as pressure transducers activating osteoblasts to induce new bone formation.
The architecture and geometry of bone is determined by its anatomic location and function. The long bones (extremities) consist mainly of cortical (compact) bone. For example, in the center of the femur, i.e. between the two joints, the bone has the shape of a hollow tube with a wall thickness of several millimeters. By contrast, near the joints of long bones and in the axial skeleton (trunk, vertebrae) bone is predominantly of the trabecular kind, consisting of a network of interconnected struts and plates fused to a surrounding relatively thin cortical shell. It is believed that this design of nature ensures optimum strength at minimum weight.
Osteoporosis (process causing “porous” bone) is a multifactorial disease leading to bone loss and architectural deterioration (see, for example, Parfitt, Bone 13:S41-47, 1992.). Whereas uniform thinning would clearly impair the trabecular network's strength, the implication of loss of connectivity through disruption of struts and plates has much more severe consequences. It has been shown, for example, that in the vertebrae, horizontal connecting trabeculae are lost preferentially during pathogenesis of osteoporosis (Mosekilde, Bone and Mineral, 10:13-35, 1990), causing the bone to fail by buckling. It is thus clear that through depletion of bone mass at critical locations in the network, loss of a small amount of bone mass can have disproportionately large mechanical consequences.
A number of laboratory studies provide compelling evidence for the contributions of trabecular architecture to the stiffness and ultimate strength of trabecular bone. A meta-analysis of 38 studies suggests that on the average about 60% of the bone's mechanical competence can be explained by variations in the apparent density (bone mass/tissue volume) alone (see, Turner, et al., J Biomechanics, 23:549-561, 1990 and Turner, et al., J Biomechanics, 25:1-9, 1992) found that density and measures of fabric (a measure of structural anisotropy) could explain up to 90% of the variance in trabecular bone's elastic constants. There is equally strong support from clinical studies for the role of architecture in conferring strength to trabecular bone (Kleerekoper, et al., Calcified Tissue International, 37:594-597, 1985) and (Legrand, et al., J. Bone Mineral Research, 15:13-19, 2000).
Most studies investigating trabecular bone architecture are based on cadaveric material or bone biopsies. The latter are typically performed at the iliac crest in the form of a cylindrical core of bone tissue being removed with a trephine (see, for example, Chavassieux, et al., Osteoporosis, 2:501-509, 2001). The specimen then is embedded in methylmethacrylate, stained and sectioned. Subsequently, the stained sections are examined by microphotography and histomorphometric parameters derived with the aid of an image analysis system. This approach, besides its invasiveness that precludes serial repeat studies in patients, is two-dimensional, although stereologic approaches enable, to a limited extent, the derivation of the third dimension (Gundersen, et al., Archives of Physical Medicine in Surgery, 96:379-394, 1988) and (Parfitt, Bone Histomorphometry: Techniques and Interpretation, Recker, Ed. Boca Raton, Fla.: CRC Press, 53-87, 1981.) More recently, bone biopsies have been imaged by micro computed tomography (μ-CT) and 3D structural measures derived from such images (see, for example, Hildebrand, et al., J Bone Miner. Res., 14:1167-74, 1999.) thus alleviating one of the limitations of this approach.
Accordingly, there is a need for a method of analyzing bone structure that overcomes all of the limitations of the current methods.